Professor Chi Chung Hui
Visiting Research Professor, School of Biomedical Sciences
The University of Hong Kong

Senior Scientist, Program in Developmental & Stem Cell Biology
The Hospital for Sick Children

Professor & Canada Research Chair, Department of Molecular Genetics
University of Toronto, Canada

Date: Monday, 29-October-2018
Time: 4:00 p.m.
Venue: Seminar Room 1, G/F, Laboratory Block,
Faculty of Medicine Building,
21 Sassoon Road, Pokfulam, Hong Kong

Summary:
SUFU alterations are common in human Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB). However, its tumorigenic mechanisms have remained elusive. Professor Hui’s group showed that loss of Sufu alone is not able to induce MB formation in mice, due to insufficient Gli2 activation. Simultaneous loss of Spop, which encodes an E3 ubiquitin ligase targeting Gli2, restores robust Gli2 activation and induces rapid MB formation in Sufu-knockout background. They also demonstrated a tumor-promoting role of Sufu in Smo-activated MB (~60% of human SHH MB) by maintaining robust Gli activity. Having established Gli2 activation as the key driver of SHH MB, they performed a comprehensive analysis of its targetome and identified Atoh1 as a target and molecular accomplice of Gli2 that activates many core SHH MB signature genes in a synergistic manner. This work establishes the dual role of SUFU in SHH MB, and provides mechanistic insights into the transcriptional regulation underlying Gli2-mediated SHH MB tumorigenesis.

ALL ARE WELCOME